Certain substituted benzisothiazoles



United States Patent 3,225,056 CERTAIN SUBSTITUTED BENZISOTHIAZOLES JohnJ. Traverso and Calvert W. Whitehead, Indianapolis, Ind., assignors toEli Lilly and Company, Indianapolis, Ind., a corporation of Indiana NoDrawing. Filed Nov. 18, 1964, Ser. No. 412,258 8 Claims. (Cl. 260--301)This invention relates to novel substituted 1,2-benzisothiazole1,1-dioxides and to methods for their preparation.

With the possible exception of saccharin, the 1,2-benzisothiazole1,1-dioxides are not well known to the chemistry of medicinal products.The art teaches certain derivatives of 6-amino-1,2-benzisothiazole1,1-dioxide as having antitubercular properties and fungicidalproperties. Other 1,2-benzisothiazole 1,1-dioxides have been found togive symptomatic relief of certain types of neuralgic, rheumatoid, andarthritic disorders. Still other examples of this type of compound showantihistaminic activity. However, substituted 1,2-benzisothiazole1,l-dioxides such as herein disclosed and possessing the new andunexpected utilities herein described have not previously been known.These novel compounds have highly useful and unexpected properties ashypotensive agents and diuretics.

A primary object of this invention is to provide novel1,2-benzisothiazo1e 1,l-dioxides differing in structure from thewell-known above-mentioned saccharin. Another object of this inventionis to provide processes for the preparation of the novel compounds.These and other objects of this invention are more fully describedhereinafter.

The novel 1,2-benzisothiazole 1,1-dioxides of this invention arerepresented by the following general formula:

X s Q N Y I ll IN=o R1 R wherein X and Y can be hydrogen, a halogen suchas chlorine, bromine, iodine, fluorine, or astatine, loweralkyl,lower-alkoxy, or trifluoromethyl; R and R when taken alone, arehydrogen; R when taken alone, is C -C alkyl or C -C alkenyl; R and Rwhen taken together with the carbon atom to which they are attached,form a cyclopentyl or cyclohexyl ring; and R and R when taken togetherwith the 1L- N= E grouping to which they are attached, form aheterocyclic ring such as pyrazole, halopyrazole, lower-alkyl pyrazole,hydroxy pyrazoline, or lower-alkyl hydroxy pyrazoline. In thisdescription, lower-alkyl is comprehended to encompass alkyl groupscontaining from one to four carbon atoms.

The following compounds are representative of the novel compounds ofthis invention:

.3- [2- (Z-butenylidene)hydrazino] -l,2-benzisothiazole 1,1-di0xide, 3-[2- (2-methyl-2-butenylidene) hydrazino] -1,2-benzisothiazole1,l-dioxide, 3-[Z-butylideuehydrazino1-l ,2-benzisothiazole 1,1-dioxide,

6-chloro-3 [2- (2-methyl-2-butenylidene) hydrazino] -1,2-

benzisothiazole 1,1-dioxide,

5,6-dimethoxy-3- [2- (Z-butenylidene hydrazino 1 ,2-

benzisothiazole 1,1-dioxide,

3-(4-bromo3,5-dimethyll-pyrazolyl) 1,2-benzisothiazole 1,1-dioxide,

3- [2-cyclohexylidenehydrazino]-1,2-benzisothiazole 1,1-

dioxide,

3- [2- Z-methyl-Z-propylidene) hydrazine] 1,2-benzisothiazole1,1-dioxide,

3( l-pyrazolyl) -1,2-benzisothiazole l,l-dioxide,

3-(3,5,S-trimethyl-Z-pyrazolin-l-yl)-1,2-benzisothiazole 1,1-dioxide,

3-(5-hydroxy-2-pyrazolin-l-yl)-1,2-benzisothiazole 1,1-

dioxide,

6-chloro-3-(1-pyrazoly1)-1,Z-benzisothiazole 1,l-dioxide,

5,6-dimethoxy-3-( l-pyrazolyl)-l,2-benzisothiazole 1,1-

dioxide,

5-methoxy-3- l-pyrazolyl) -l,2-benzisothiazole 1,1di-

oxide,

5-chloro-3-(l-pyrazolyl)-1,2-benzisothiazole l,l-dioxide,

6-fiuoro-3- l-pyrazolyl) 1,2-benzisothiazole 1,1-dioxide,

5-trifiuoromethyl-3-( l-pyrazolyl) -1,2- benzisothiazo1e 1,1-dioxide,

3- (4-chloro-1-pyrazo1yl) -l ,2-benzisothiazo1e 1,1-dioxide,

3-(3,4,5-trimethyl-l-pyrazolyl)-l,2-benzisothiazole 1,1-

dioxide,

3(3,5-dimethyl l-pyrazolyl) -1,2-benzisothiazole 1,1-

dioxide,

3-(3,5-diethyl-1-pyrazolyl)-1,2-benzisothiazole 1,1-dioxide,

and the like.

From the above description and examples, it can be seen that the novel1,2-benzisothiazole 1,l dioxides of this invention are markedlydifferent in structure from the prior-art compound saccharin. Thecompounds of this invention have either a substituted hydrazine moietyor, alternatively, a pyrazole, substituted pyrazole, or pyrazolinylradical, attached at the 3-position of the benzisothiazole nucleus;there is additional unsaturation in the isothiazole ring; and varioussubstituents may be found attached to the benzenoid portion of themolecule.

The structural differences above described result in a most unusualseries of compounds, a series which exhibits significant hypotensiveactivity and interesting diuretic activity.

The novel compounds of this invention are conveniently preparedutilizing as one of the starting reagents a 3-substituted1,2-benzisothiazole 1,1-dioxide represented by the following formula:

X so2 Y wherein X and Y have the same significance as hereinbefore, andZ is halogen or hydrazine. These starting benzisothiazoles are readilysynthesized by methods well known to the art.

The 3 (substituted hydrazino)benzisothiazole compounds of this invention(Formula I, hereinabove) may be obtained by any one of severalprocesses. One method comprises commingling a3-hydrazino-l,2-benzisothiazole 1,1dioxide or a substituted3-hydrazino-l,2- benzisothiazole 1,1-dioxide with an appropriatecarbonyl compound, suitably an aliphatic or cycloaliphatic alde hyde orketone, in an inert organic mutual solvent such as dioxane, ethanol,propanol, Cellosolve, or the like, and heating the reaction mixture to atemperature in the range from about 40 to about 130 C., suitably around60 to 100 C., preferably at the reflux temperature of the reactionmixture, for a period of time suflicient to produce a substantial yieldof the desired condensation product. After cooling the reaction productmixture to room temperature, the solid material contained therein isconveniently filtered off. It is recrystallized from a suitable organicsolvent such as methanol, ethanol, ethyl acetate, or, in some cases,water, to yield a 3(substi tuted hydrazino) 1,2 benzisothiazole 1,1dioxide. Compounds of the present invention which may be preparedaccording to this process include:

3- [2-(2-methyl-2-butenylidene)hydrazino]-1,2-benzisothiazole1,1-dioxide;

6-chloro-3- [2-(2-methyl-2-butenylidene )hydrazino] -1,2-

benzisothiazole 1,1-dioxide;

5,6-dimethoxy-3 2- methyl-2-butenylidene) hydrazino]-l,2-benzisothiazole1,1-dioxide;

3- 2-butylidenehydrazino 1,2-benzisothiazole 1,1-dioxide;

3-(2-cyclohexylidenehydrazino)-1,2-benzisothiazole 1,1-

dioxide, and the like.

The heterocyclic-substituted benzisothiazoles of Formula I, supra, anddescribed herein, can be conveniently prepared in several ways. Onesuitable method consists of heating a mixture of3-chloro-1,2-benzisothiazole 1,1-dioxide and two equivalents of, forexample, pyrazole, in the solid state, in the absence of a solvent. Thesecond mole of pyrazole acts to take up hydrogen halide formed duringthe reaction and may be suitably replaced by a tertiary amine such astriethylamine, pyridine, tripropylamine, or the like. Highertemperatures may be employed when the reaction is thus carried out inthe absence of a solvent, and sublimation of pyrazole during thereaction may readily be avoided by careful adjustment of the reactionmixture temperature. The reaction, which is exothermic, requires carefulcontrolfThe reaction product mixture is conveniently worked up bywashing it with water to remove the undesired by-product pyrazole salt,collecting the waterinsoluble residue on a filter, and recrystallizingthe residue from a suitable solvent such as ethyl acetate to yield thedesired product (e.g., 3-(1-pyrazolyl)-1,2-benzisothiazole 1,1-dioxidefrom pyrazole).

The same type of condensation can be accomplished using an inert organicmutual solvent such as benzene, dioxane, toluene, and the like, fordissolving the halobenzisothiazole and the pyrazole reactants. In thiscase, when the reaction is complete, the reaction product mixture may bereadily concentrated in vacuo to leave a residue, which isrecrystallized from a suitable solvent such as ethyl acetate to yieldthe heterocyclic-substituted 1,2-benzisothiazole 1,1-dioxide.

Another method for preparing a pyrazole-substituted benzisothiazolecomprises allowing a mixture of, for example, tetraethoxypropane,3-hydrazino-1,2-benzisothiazole 1,1-dioxide, water, and a small amountof sulfuric acid to react at about ambient room temperature for a periodof several hours.- The reaction mixture first becomes homogeneous andthen the intermediate product, 3 (5 hydroxypyrazolin 1 yl) 1,2benzisothiazole 1,1-dioxide crystallizes out of the solution. Theintermediate product is conveniently filtered otf. It can be readilydehydrated by heating with a dehydrating agent such as acetic anhydrideor trifluoroacetic acid, at steambath temperature. The reaction productmixture can be concentrated in vacuo to leave a residue which isrecrystallized from a suitable solvent such as ethyl acetate to yield3-(l-pyrazolyl)-1,2-benzisothiazole 1,1-dioxide.

In some cases a solvent other than water is conveniently used in thepreparation described in the previous paragraph. For example, thereaction may be carried out by allowing a mixture of dipropionylmethane, 3-hydrazino-1,2-benzisothiazole 1,1-dioxide, and an inertorganic mutual solvent such as Cellosolve to react at the refluxtemperature of the mixture for several hours. The solvent is removedfrom the reaction product mixture in vacuo, and the residue remaining isrecrystallized from ethyl acetate to yield the intermediate product,3-(3,5- diethyl-S-hydroxypyrazolin-l-yl)-1,2-benz1soth1azole 1,1dioxide. This intermediate compound can be then conveniently dehydratedas described hereinabove, to y1eld 3 (3,5 diethyl-l pyrazolyl) 1,2benzisothiazole 1,1-dioxide.

Other compounds of the present invention which may be prepared accordingto the above processes lnclude 3-( l-pyrazolyl)-1,2-benzisothiazole 1,1-dioxide,

3-(3,5-dimethyl-l-pyrazolyl)-1,2-benz1soth1azole 1,1-

dioxide,

6-chloro-3-( l-pyrazolyl)-l,2benzisothiazole 1,1-d1ox1de,

5,6-dimethoxy-3-( l-pyrazolyl) -1,2-'benzisothiaz-ole 1,1-

dioxide,

and the like.

While the above discussion of novel compounds mentions only pyrazole orsubstituted pyrazole radicals as substituents in the 3-position of thebenzisothiazole nucleus, the invention is envisioned as including allcompounds obtained by allowing the reaction of3-chloro-1,2-benz1sothiazone 1,1-dioxide with nitrogen containingheterocycles such as imidazoles, triazoles, oxadiazines, oxatriazines,thiadiazines, thiatriazines, azepines, diazepines, and the like,sufficiently basic in character to react therewith.

That the invention may be more easily comprehended, examples of thesynthesis of compounds comlng within the scope of the invention aregiven hereinbelow.

EXAMPLE 1 3- [2-(Z-methyl-Z-butenylidene) hydrazino] -1 ,2-benzis0-thiazole 1,1-dioxide.A mixture of 19.7 g. (0.10 mole) of3-hydrazino-1,Z-benzisothiazole 1,1-dioxide and 12.6 g. (0.15 mole) oftiglaldehyde in 200 ml. of dioxane was refluxed for about two hours. Thereaction product mixture was cooled to room temperature and the solidproduct was filtered 01f. Crystallization of the solid product frommethanol yielded '3-[2-(2-methyl2butenylidene)hydrazino]-1,2-benzisothiazole 1,1-dioxide having a meltingpoint of about 250 C. (d.). Yield: 20.3 g. (77 percent of theory).

Analysis.-Calcd: C, 54.73; H, 4.97; N, 15.96. Found: C, 54.80; H, 5.14;N, 16.06.

EXAMPLE 2 6-chlor0-3-[2-(2-methyl 2 butenylidene)hydrazine]-1,2-benzisothiazole J ,1 -di0xide.Following the procedure of Example 1,but using 4 g. (0.017 mole) of 6-chloro-3- hydrazino-l,Z-benzisothiazone1,1-dioxide and 2 g. (0.024 mole of tiglaldehyde as reactants,6-chloro-3-[2-(2-methyl- Z-butenylidene) hydrazino-1,2-benzisothiazole1,1-dioxide was obtained as a solid having a melting point of about 250C. (d.) after recrystallization from methanol. Yield: 2.5 g. (71 percentof theory).

Analysis.-Calcd: C, 48.40; H, 4.06; N, 14.11. Found: C, 48.43; H, 4.28;N, 13.99.

EXAMPLE 3 5,6-dimezh0xy-3-[Z-(Z-meth l 2 butenylidene)hydrazin01-1,Z-benzisothiazole 1,1-di0xide.Following the procedure of Example 1, butusing 1.36 g. (0.0053 mole) of5,6-dimethoxy-3-hydrazino-1,2-benzisothiazole 1,1-dioxide and 1 g.(0.012 mole) of tiglaldehyde as reactants, 5,6- dimethoxy-3-[2-(2-methyl2 butenylidene)hydrazino]- 1,2-benzisothiazole 1,1-dioxide was obtainedhaving a melting point of about 230 C. (d.) after recrystallization frommethanol. Yield: 0.4 g. (23 percent of theory);

AnaZysis.-Calcd: C, 52.00; H, 5.30; N, 13.00. Found: C, 51.89; H, 5.44;N, 12.74.

,5. EXAMPLE 4 3-(Z-butylidenehydrazino) 1,2 benzisothiazole 1,1-dixide.'Following the procedure of Example 1, but using 19.7 g. (0.10mole) of 3-hydrazino-1,2-benzisothiazole 1,1-dioxide and 10 g. (0.14mole) of n-butyraldehyde as reactants,3-(Z-butylidenehydraZino)-1,2-benzisothiazole 1,1-dioxide was obtainedas a crystalline product having a melting point of about 95 C. and foundby analysis to contain one molecule of Water of crystallization. Yield:10 g. (40 percent of theory).

Analysis.Calcd: C, 49.05; H, 5.61; N, 15.60. Found: C, 50.10; H, 5.84;N, 15.24.

EXAMPLE 5 3-[Z-(Z-butenylidene)hydrazino] 1,2 benziso ihiazole1,]-di0xide.--Following the procedure of Example 1, but using g. (0.05mole) of 3-hydrazino-1,2-benzisothiazole 1,1-dioxide and 100 ml. (excessas solvent) of cr-otonaldehyde as reactants,3-[Z-(Z-butenylidene)hydrazino]-1,2- benzisothiazole 1,1-dioxide wasobtained as a solid having a melting point of about 186 C. afterrecrystallization from methanol. Yield: 9.5 g. (76 percent of theory).

Analysis.Calcd: C, 52.99; H, 4.44; N, 16.86. Found: C, 52.29; H, 4.75;N, 16.53.

EXAMPLE 6 3- [2-(Z-metlzyl-2-propylidene) hydrazino] -1,2 benziothiazole l,l-dioxide.-Following the procedure of Example 1, but using25 g. (0.127 mole) of 3-hydrazino-1,2- benzisothiazole 1,1- dioxide and25 g. (0.32 mole) of a 90 percent aqueous solution ofa-methylacrylald-ehyde as reactants, 3- 2-methyl-2-propylidene)-hydr-a2ino] 1 ,2- benzisothiazole 1,1-dioxide was obtained as a solidhaving a melting point of about 211 C. after recrystallization frommethanol. Yield: 20 g. (63.5 percent of theory).

Analysis.-Calcd: C, 53.21; H, 4.05; N, 16.92. Found: C, 53.74; H, 4.72;N, 17.30.

EXAMPLE 7 3- (2-cycl0hexylidenehydrazino)-1,2-benzisothiazole 1,1-dioxide.-Following the procedure of Example 1, but using 10 g. (0.05mole) of 3-hydrazino-1,2-benzisothiazole 1,1-dioxide and 4.97 g. (0.05mole) of cyclohexanone as reactants, 3-(2-cyclohexylidenehydrazino)1,2-benzisothiazole 1,1-dioxide was obtained as a solid having a meltingpoint of about 178 C. after recrystallization from ethyl acetate. Yield:2 g. (14.5 percent of theory).

AnaIysis.-Calcd: C, 56.29; H, 5.45; N, 15.15. Found: C, 55.96; H, 5.88;N, 14.79.

EXAMPLE 8 3-(] -pyraz0lyl -J ,Z-benzisothiazole J ,1 -di0xide.Step A. Toa rapidly stirred suspension composed of 20 g. (0.1 mole) of3-hydrazino-1,2-benzisothiazole 1,1-dioxide, 250 ml. of Water, and 30 g.(0.136 mole) of tetraethoxypropane were added rapidly dropwise 8 g.(0.076 mole) of concentrated sulfuric acid. The reaction mixture wasstirred at room temperature for several hours, during which time themixture became homogeneous, and a solid subsequently crystallizedtherefrom. The reaction product mixture was filtered and the solid thuscollected, which weighed 22 g. (87 percent of theory) was recrystallizedfrom ethyl acetate to yield 3-(S-hydroxypyrazolin-1-yl)-1,2-benzisothiazole 1,1-dioxide as a solid having a melting point ofabout 217 C.

Analysis.Calcd: C, 47.80; H, 3.61; N, Found: C, 47.79; H, 3.86; N,16.73.

Step B. A mixture of 96 g. (0.385 mole) of3-(5-hydroxypyrazolin-1-yl)1,Z-benzisothiazole 1,1-dioxide and 700 ml,of acetic anhydride was heated on the steam bath for about 3 hours. Theunreacted acetic anhydride was distilled from the reaction productmixture in vacuo and the residue was recrystallized from ethyl acetateto yield 3-(1-pyrazolyl)-1,2-benzisothiazole 1,1-dioxide as a solidzation from ethyl acetate.

6 having a melting point of about 220 C. Yield: 50.5 g. (54.5 percent oftheory).

Analysis.Calcd: C, 51.49; H, 3.03; N. 1.8.02. Found: C, 51.72; H, 3.28;N, 17.60.

EXAMPLE 9 3-(3,5-diethyl-J-pyrazolyl)-1,2-benzis0thiaz0le 1,1-dioxide.-Amixture composedof 20 g. (0.1 mole) of 3-hydrazino-l,Z-benzisothiazole1,1-dioxide, 20 g. (0.156 mole) of dipropionylmethane, and ml. ofCellosolve was refluxed for several hours. The reaction product mixturewas concentrated in vacuo to remove the solvent. The residue remainingwas recrystallized from ethyl acetate to yield3-(3,5-diethyl-5-hydroxypyrazolin-l-yl)- 1,2-benzisothiazole 1,1-dioxideas a solid having a melting point of about 189 C. Yield: 23 g. (79.5percent of theory),

Analysis.-Calcd. C, 54.70; H, 5.57; N, 13.67; 0, 15.62. Found: C, 54.79;H, 5.61; N, 14.01; 0, 15.63.

Following the procedure of Example 8, Step B, the3-(3,5-diethyl-5-hydroxypyrazolin-1-yl) 1,2-benzisothiazole,1,1-dioxide, 20 g. (0.08 mole), was reacted with acetic anhydride indioxane and 3-(3,5-diethyl-1-pyrazolyl)-1,2benzisothiazole 1,1-dioxanewas obtained as a solid having a melting point of about 140 C. afterrecrystalli- Yield: 10 g. (42 percent of theory).

Analysis.--Calcd: C, 58.11; H, 5.22; N, 14.52. Found: C, 57.98; H, 5.25;N, 14.26.

EXAMPLE 10 3-(3,5,5-trimethyl-2-pyraz0lin-1-yl) 1,2 benzisothiazolel,]-dioxide.A mixture of 10 g. (0.0.5 mole) of 3-hydrazino-1,2-benzisothiazole 1,1-dioxide and 100 ml. of redistilledmesityl oxide was heated on the steam bath for several hours, duringwhich time complete solution occurred. The reaction product mixture wasconcentrated under reduced pressure in order to remove unreacted mesityloxide. The residue was recrystallized from ethyl acetate to yield3-(3,5,5-trimethyl-2-pyrazolin-1-yl)-1,2- benzisothiazole 1,1-dioxide asa solid having a melting point of about 198 C. Yield: 5 g. (40 percentof theory).

Analysis.Calcd: C, 56.29; H, 5.45; N, 15.15. Found: C, 56.06; H, 5.52;N, 14.88.

EXAMPLE 11 3-(3,5-dimethylal-pyrazolyl)-1,2-benzis0thiaz0le1,1-dioxide.-Following the procedure of Example 10 but using 5 g. (0.025mole) of 3-hydrazino-1,2-benzisothiazole 1,1- dioxide and2,4-pentanedione, in large excess, as reactants,3-(3,5-dimethyl-1-pyrazolyl)-1,2 benzisothiazole 1,1-dioxide wasobtained as a solid having a melting point of about 191 C. afterrecrystallization from ethanol. Yield: 4 g. (61.5 percent of theory).

Analysis.-Calcd: C, 55.15; H, 4.24; N, 16.08. Found: C, 55.40; H, 4.48;N, 15.74.

EXAMPLE 12 3-(3,4,5-trimethyl-l-pyrazolyl-I,2benzis0thiaz0le 1,1-dioxide.--A mixture of 10 g. (0.05 mole) of 3-.hydrazino-1,2-benzisothiazole 1,1-dioxide and 5.8 g. (0.05 mole) of3-methy1-2,4-pentanedione in 80 ml. of dioxane was refluxed for about 18hours. The reaction product mixture was concentrated in vacuo to removethe solvent, and the residue was recrystallized from ethyl acetate, toyield 3-(3,4,5-trimethyl-5-hydroxypyrazolin-1 yl)-1,2-benzisothiazole1,1-dioxide as a solid having a melting point of about -180" C. Yield: 4g. (27.3 percent of theory).

Analysis.Calcd: C, 53.24; H, 5.16; N, 14.33. Found: C, 53.97; H, 5.13;N, 14.77.

A mixture of 2 g. (0.007 mole) of 3-(3,4,5-trimethyl-S-hydroxypyrazolin-l-yl)-1,2-benzisothiazole 1,1-dioxide and 75 ml. ofacetic anhydride was heated for about 5 hours on the steam bath. Thereaction product mixture 7 was concentrated in vacuo and the residuethereby obtained was recrystallized from ethyl acetate to yield 3-(3,4-S-trimethyl-1-pyrazolyl)-1,2 benzisothiazole 1,1-dioxide as a solidhaving a melting point of about 273 C. Yield: 1.1 g. (57 percent oftheory).

Analysis.-Calcd: C, 56.71; H, 4.75; N, 15.26. Found: C, 56.52; H, 4.73;N, 14.89.

EXAMPLE 13 3-(4-chlor0J-pyraz0lyl) 1,2 benzisothiazole 1,1-a'ixide.Amixture of g. (0.05 mole) of 3-ch1oro-1,2- benzisothiazole 1,1-di0xideand 11.2 (0.11 mole) of 4-chloropyrazole was fused in a flask in an oilbath and maintained .at that temperature for about 2 hours. The reactionproduct mixture was cooled and washed with cold water, whereupon itsolidified. The solid material vwas filtered off and the filtratediscarded. The solid was then recrystallized from dry benzene to yield3-(4-chlorol-pyrazolyl)-1,2-benzisothiazole 1,1-dioxide as a solidhaving a melting point of about 145 C. Yield: 4 g. (31 percent oftheory).

Analysis.Calcd: C, 44.86; H, 2.25; N, 15.70. Found: C, 45.17; H, 2.48;N, 15.63.

EXAMPLE 14 3-(4-br0m0-3,5-dimethyl 1 pyrazolyl) 1,2-benzisothiazole1,1-di0xide.A solution of 26 g. (0.10 mole) of3-(3,5-dimethyl-1-pyrazolyl)-1,2-benzisothiazole 1,1- dioxide in 300 ml.of chloroform was allowed to react with 16 g. (0.1 mole) of bromine fora period of about 12 hours at ambient room temperature. The reactionproduct mixture was concentrated by evaporating the solvent on the steambath to leave a residue. The residue was recrystallized from ethylacetate to yield 3-(4-bromo- 3,S-dimethyl-l-pyrazolyl)-1,Z-benzisothiazole 1,1-dioxide as a solidhaving a melting point of about 250 C. (d.). Yield: 26 g. (76.5 percentof theory).

Analysis.Calcd: C, 42.36; H, 2.96; N, 12.35. Found: C, 42.53; H, 3.25;N, 12.37.

8 We claim: 1. The compounds having the following formula X SO:

N R2 Y 1?TN=CR1 wherein R and R when taken alone, are hydrogen; R whentaken alone, is selected from the group consisting of C -C alkyl, and C-C alkenyl; X and Y are selected from the group consisting of hydrogen,halogen, lower alkyl, trifiuoromethyl, and lower alkyloxy; R and R whentaken together with the carbon atom to which they are attached, form C-C cycloalkyl; and R and R when taken together with the I I NN=Cgrouping to which they are attached, form a heterocyclic ring selectedfrom the group consisting of pyrazole, halopyrazole, lower-alkylpyrazole, hydroxypyrazoline, and lower-alkyl hydroxy pyrazoline.

2. 3-[2 (2 methyl 2 butenylidene)hydrazino]-1,2- benzisothiazole1,1-dioxide.

3. 6-ch1oro 3 [2 (2-methyl-2-butenylidene)hydrazino]-1,2-benzisothiazole1,1-dioxide.

4. 5,6-dimethoxy-3-[2-(2-metliyl 2butenylidene)hydrazino]-1,2-benzisothiaz0le 1,1-dioxide.

5. 3-(l-pyrazolyl)-1,2-benzisothiazole 1,1-dioxide.

6. 3-(3,5-dimethy1-l-pyrazolyl) 1,2 benzisothiazole 1,1-dioxide.

7. 3-(3,5,5-trimethyl 2 pyrazoline-1-yl)-l,2-benziso thiazole1,1-dioxide.

8. 3-(5-hydroxy-2-pyrazoline-l-yl) 1,2-benzisothiazole 1,1-dioxide.

No references cited.

NICHOLAS S. RIZZO, Primary Examiner.

1. THE COMPOUNDS HAVING THE FOLLOWING FORMULA